Immunotherapy and associated immune regulation strategies gained huge attraction in order to be utilized for treatment and prevention of respiratory diseases.Engineering specifically nanomedicines can be used to regul...Immunotherapy and associated immune regulation strategies gained huge attraction in order to be utilized for treatment and prevention of respiratory diseases.Engineering specifically nanomedicines can be used to regulate host immunity in lungs in the case of respiratory diseases including coronavirus disease 2019(COVID-19)infection.COVID-19 causes pulmonary embolisms,thus new therapeutic options are required to target thrombosis,as conventional treatment options are either not effective due to the complexity of the immunethrombosis pathophysiology.In this review,we discuss regulation of immune response in respiratory diseases especially COVID-19.We further discuss thrombosis and provide an overview of some antithrombotic nanoparticles,which can be used to develop nanomedicine against thrombo-inflammation induced by COVID-19 and other respiratory infectious diseases.We also elaborate the importance of immunomodulatory nanomedicines that can block pro-inflammatory signalling pathways,and thus can be recommended to treat respiratory infectious diseases.展开更多
Nanomedicines employ multiple endocytic pathways to enter cells.Their following fate is interesting,but it is not sufficient understood currently.This review introduces the endocytic pathways,presents new technologies...Nanomedicines employ multiple endocytic pathways to enter cells.Their following fate is interesting,but it is not sufficient understood currently.This review introduces the endocytic pathways,presents new technologies to confirm the specific endocytic pathways and discusses factors for pathway selection.In addition,some intriguing implication about nanomedicine design based on endocytosis will also be discussed at the end.This review may provide new thoughts for the design of novel multifunctional nanomedicines.展开更多
Tumor cell usually exhibits high levels of reactive oxygen species and adaptive antioxidant system due to the metabolic,genetic,and microenvironment-associated alterations.The altered redox homeostasis can promote tum...Tumor cell usually exhibits high levels of reactive oxygen species and adaptive antioxidant system due to the metabolic,genetic,and microenvironment-associated alterations.The altered redox homeostasis can promote tumor progression,development,and treatment resistance.Several membrane transporters are involved in the resetting redox homeostasis and play important roles in tumor progression.Therefore,targeting the involved transporters to disrupt the altered redox balance emerges as a viable strategy for cancer therapy.In addition,nanomedicines have drawn much attention in the past decades.Using nanomedicines to target or reset the redox homeostasis alone or combined with other therapies has brought convincing data in cancer treatment.In this review,we will introduce the altered redox balance in cancer metabolism and involved transporters,and highlight the recent advancements of redox-modulating nanomedicines for cancer treatment.展开更多
In recent years,nanomedicine plays an increasingly important role in improving the effectiveness,accuracy and safety of disease diagnosis and treatment.Happily,some of these nanoparticles are in clinical trials or hav...In recent years,nanomedicine plays an increasingly important role in improving the effectiveness,accuracy and safety of disease diagnosis and treatment.Happily,some of these nanoparticles are in clinical trials or have been approved by the Food and Drug Administration.With the deepening of research,people’s understanding of the interaction between nanomedicine and body system is increasing,and a new generation of biomimetic nanomedicine platforms has been developed to further improve the treatment effect of diseases.In this review,we will discuss recent advances in biomimetic nanosystems for the treatment of diseases,including cardio-cerebrovascular diseases,diabetes,and cancer.We hope that there will be more advanced biomimetic nanomedicines that can be widely used in the treatment of diseases in the future.展开更多
Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune response.Numerous therapeutic strategies in...Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune response.Numerous therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune response.However,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic response.Here,we outline the current state of using nanomedicines for boosting ICD of cancer cells.Moreover,synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were analyzed.We further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune responses.Endoplasmic reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicines,amplified reactive oxygen species(ROS)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative approaches.Various challenges,merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.展开更多
Lipid-based nanomedicines(LBNMs),including liposomes,lipid nanoparticles(LNPs)and extracellular vesicles(EVs),are recognized as one of the most clinically acceptable nano-formulations.However,the bench-to-bedside tran...Lipid-based nanomedicines(LBNMs),including liposomes,lipid nanoparticles(LNPs)and extracellular vesicles(EVs),are recognized as one of the most clinically acceptable nano-formulations.However,the bench-to-bedside translation efficiency is far from satisfactory,mainly due to the lack of in-depth understanding of their physical and biochemical attributes at the single-particle level.In this review,we first give a brief introduction of LBNMs,highlighting some milestones and related scientific and clinical achievements in the past several decades,as well as the grand challenges in the characterization of LBNMs.Next,we present an overview of each category of LB-NMs as well as the core properties that largely dictate their biological characteristics and clinical performance,such as size distribution,particle concentration,morphology,drug encapsulation and surface properties.Then,the recent applications of several analytical techniques including electron microscopy,atomic force microscopy,fluorescence microscopy,Raman microscopy,nanoparticle tracking analysis,tunable resistive pulse sensing and flow cytometry on the single-particle characterization of LBNMs are thoroughly discussed.Particularly,the com-parative advantages of the newly developed nano-flow cytometry that enables quantitative analysis of both the physical and biochemical characteristics of LBNMs smaller than 40 nm with high throughput and statistical ro-bustness are emphasized.The overall aim of this review article is to illustrate the importance,challenges and achievements associated with single-particle characterization of LBNMs.展开更多
Atherosclerosis(AS)is a leading cause of the life-threatening cardiovascular disease(CVD),creating an urgent need for efficient,biocompatible therapeutics for diagnosis and treatment.Biomimetic nanomedicines(b NMs)are...Atherosclerosis(AS)is a leading cause of the life-threatening cardiovascular disease(CVD),creating an urgent need for efficient,biocompatible therapeutics for diagnosis and treatment.Biomimetic nanomedicines(b NMs)are moving closer to fulfilling this need,pushing back the frontier of nano-based drug delivery systems design.This review seeks to outline how these nanomedicines(NMs)might work to diagnose and treat atherosclerosis,to trace the trajectory of their development to date and in the coming years,and to provide a foundation for further discussion about atherosclerotic theranostics.展开更多
The complexity of the tumor microenvironment(TME)severely hinders the therapeutic effects of various cancer treatment modalities.The TME differs from normal tissues owing to the presence of hypoxia,lowpH,and immunesup...The complexity of the tumor microenvironment(TME)severely hinders the therapeutic effects of various cancer treatment modalities.The TME differs from normal tissues owing to the presence of hypoxia,lowpH,and immunesuppressive characteristics.Modulation of the TME to reverse tumor growth equilibrium is considered an effective way to treat tumors.Recently,polymeric nanomedicines have been widely used in cancer therapy,because their synthesis can be controlled and they are highly modifiable,and have demonstrated great potential to remodel the TME.In this review,we outline the application of various stimuli responsive polymeric nanomedicines to modulate the TME,aiming to provide insights for the design of the next generation of polymeric nanomedicines and promote the development of polymeric nanomedicines for cancer therapy.展开更多
Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment,nanomedicine designs have received widespread attention with significa...Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment,nanomedicine designs have received widespread attention with significantly improved efficacy and reduced non-target side effects.Nanomedicines hold tremendous theranostic potential for treating,monitoring,diagnosing,and controlling various diseases and are attracting an unfathomable amount of input of research resources.Against the backdrop of an exponentially growing number of publications,it is imperative to help the audience get a panorama image of the research activities in the field of nanomedicines.Herein,this review elaborates on the development trends of nanomedicines,emerging nanocarriers,in vivo fate and safety of nanomedicines,and their extensive applications.Moreover,the potential challenges and the obstacles hindering the clinical translation of nanomedicines are also discussed.The elaboration on various aspects of the research trends of nanomedicines may help enlighten the readers and set the route for future endeavors.展开更多
Sepsis is the leading cause of death in intensive care unit(ICU), which is caused by deregulated immune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and supportive care, whi...Sepsis is the leading cause of death in intensive care unit(ICU), which is caused by deregulated immune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and supportive care, while there still lacks of specific molecular therapy. As a type of immune dysfunction disease,macrophages have been recognized as the key immune cells precipitating in the whole process of sepsis,which is activated into M1-like to trigger various inflammatory responses at early stage whereas polarized into M2-like to cause immunosuppression in later stage. Therefore, great attention has been paid on the design of nanomedicines to regulate the functions of macrophages for etiological treatment of sepsis, by virtue of the unique advantages of nano-drug delivery systems, such as enhanced drug bioavailability, targetability, reduced side-effects. This critical review aims to summarize the recent progress of macrophages-regulating nanoparticles for sepsis therapy. First, the essential roles of macrophages in the development and progression of sepsis have been introduced, including the positive roles of macrophages to combat infections and dysfunction of macrophages to cause body damages. We then focus our main attention to discuss the nanomedicines with different therapeutic mechanisms corresponding to each stage of sepsis, such as infection blockage, inflammation inhibition, immune functions recovery, as well as multifunctional nanomedicines. Finally, a few limitations of current nanomedicines are highlighted,and future perspective are speculated for potential clinical translation, which might pave the way for the development of macrophages-centered nanomedicines for more effective sepsis therapy.展开更多
Nanomedicines have shown great promise in cancer therapy,but are challenged by limited drug loading,safety concerns of drug carriers,and complexity of function integration.Recently,carrier-free nanomedicines produced ...Nanomedicines have shown great promise in cancer therapy,but are challenged by limited drug loading,safety concerns of drug carriers,and complexity of function integration.Recently,carrier-free nanomedicines produced by supramolecular assembly of small-molecule therapeutic functionalities and their conjugates were proposed to address these issues.These nanomedicines achieve very high drug loading,enhanced tumor accumulation and improved therapeutic efficiency,and avoid carrier-related safety problems.In this review article,the applications of these nanomedicines in chemotherapy,photodynamic therapy,photothermal therapy as well as combination therapies will be reviewed.The concept of nanomedicine design and mechanism of supramolecular assembly will be discussed.Finally,future perspectives of carrier-free supramolecular nanomedicines for cancer therapy will be highlighted.展开更多
RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases.These include antisense oligonucleotides(ASOs),s...RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases.These include antisense oligonucleotides(ASOs),small interfering RNAs(siRNAs),endogenous microRNAs(miRNAs),messenger RNAs(mRNAs),clustered regularly interspersed short palindromic repeats-associated protein 9(CRISPR/Cas9),single guide RNAs(sgRNAs),as well as RNA aptamers.These therapeutic agents exert their effects through various mechanisms such as gene inhibition,addition,replacement,and editing.The advancement of RNA biology and the field of RNA therapy has paved the way for the development and utilization of RNA-based nanomedicine in human healthcare.One remarkable example of RNA-based nanomedicine is the mRNA-based vaccines including mRNA-1273(Moderna)and BNT162b2(Pfizer/BioNTech)that have been successfully employed in response to the coronavirus disease 2019(COVID-19)pandemic.This review aims to highlight the advantages of RNA-based nanomedicines,provides an overview of significant developments in delivery systems,elucidates the molecular mechanisms of action underlying RNA-based nanomedicines,and discusses their clinical applications.Additionally,the review will address the existing challenges and innovations in delivery platforms while exploring the future possibilities for these promising RNA-based nanomedicines.展开更多
Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation ene...Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.展开更多
Cancer immunotherapy has significantly flourished and revolutionized the limited conventional tumor therapies,on account of its good safety and long-term memory ability.Discouragingly,low patient response rates and po...Cancer immunotherapy has significantly flourished and revolutionized the limited conventional tumor therapies,on account of its good safety and long-term memory ability.Discouragingly,low patient response rates and potential immune-related side effects make it rather challenging to literally bring immunotherapy from bench to bedside.However,it has become evident that,although the immunosuppressive tumor microenvironment(TME)plays a pivotal role in facilitating tumor progression and metastasis,it also provides various potential targets for remodeling the immunosuppressive TME,which can consequently bolster the effectiveness of antitumor response and tumor suppression.Additionally,the particular characteristics of TME,in turn,can be exploited as avenues for designing diverse precise targeting nanomedicines.In general,it is of urgent necessity to deliver nanomedicines for remodeling the immunosuppressive TME,thus improving the therapeutic outcomes and clinical translation prospects of immunotherapy.Herein,we will illustrate several formation mechanisms of immunosuppressive TME.More importantly,a variety of strategies concerning remodeling immunosuppressive TME and strengthening patients'immune systems,will be reviewed.Ultimately,we will discuss the existing obstacles and future perspectives in the development of antitumor immunotherapy.Hopefully,the thriving bloom of immunotherapy will bring vibrancy to further exploration of comprehensive cancer treatment.展开更多
Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with ...Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages,but it is often ineffective and suffers from problems such as multidrug resistance,rapid drug clearance,nonspecific targeting,high side effects,and low drug accumulation in tumor cells.In response to these limitations,recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC.This review focuses on recent advances in nanoparticle-based targeted drug delivery systems,with special attention to various receptors overexpressed on HCC cells.These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC.We comprehensively summarize the current understanding of these receptors,their role in nanoparticle targeting,and the impact of such targeted therapies on HCC.By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies,more effective and precise treatment of HCC can be achieved.展开更多
Increasing understanding of the pathogenesis of rheumatoid arthritis(RA)has remarkably promoted the development of effective therapeutic regimens of RA.Nevertheless,the inadequate response to current therapies in a pr...Increasing understanding of the pathogenesis of rheumatoid arthritis(RA)has remarkably promoted the development of effective therapeutic regimens of RA.Nevertheless,the inadequate response to current therapies in a proportion of patients,the systemic toxicity accompanied by longterm administration or distribution in non-targeted sites and the comprised efficacy caused by undesirable bioavailability,are still unsettled problems lying across the full remission of RA.So far,these existing limitations have inspired comprehensive academic researches on nanomedicines for RA treatment.A variety of versatile nanocarriers with controllable physicochemical properties,tailorable drug release pattern or active targeting ability were fabricated to enhance the drug delivery efficiency in RA treatment.This review aims to provide an up-to-date progress regarding to RA treatment using nanomedicines in the last 5 years and concisely discuss the potential application of several newly emerged therapeutic strategies such as inducing the antigen-specific tolerance,pro-resolving therapy or regulating the immunometabolism for RA treatments.展开更多
Compared with traditional drug therapy,nanomedicines exhibit intriguing biological features to increase therapeutic efficiency,reduce toxicity and achieve targeting delivery.This review provides a snapshot of nanomedi...Compared with traditional drug therapy,nanomedicines exhibit intriguing biological features to increase therapeutic efficiency,reduce toxicity and achieve targeting delivery.This review provides a snapshot of nanomedicines that have been currently launched or in the clinical trials,which manifests a diversified trend in carrier types,applied indications and mechanisms of action.From the perspective of indications,this article presents an overview of the applications of nanomedicines involving the prevention,diagnosis and treatment of various diseases,which include cancer,infections,blood disorders,cardiovascular diseases,immuno-associated diseases and nervous system diseases,etc.Moreover,the review provides some considerations and perspectives in the research and development of nanomedicines to facilitate their translations in clinic.展开更多
Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics.However,direct administration of“naked”immunotherapeutic agents(such as nucleic aci...Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics.However,direct administration of“naked”immunotherapeutic agents(such as nucleic acids,cytokines,adjuvants or antigens without delivery vehicles)often results in:(1)an unsatisfactory efficacy due to suboptimal pharmacokinetics;(2)strong toxic and side effects due to low targeting(or off-target)efficiency.To overcome these shortcomings,a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects.Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties,as they could interact with immune system to stimulate an enhanced immune response.Their structures offer versatility in synthesizing multifunctional nanocomposites,which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues.This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics.展开更多
Ferroustherapy has gained great attention for anti-cancer treatment in recent years. Enlightened by temperature-mediated Fenton reaction in industrial waste water removal, we designed a iron-based polyphenol-coordinat...Ferroustherapy has gained great attention for anti-cancer treatment in recent years. Enlightened by temperature-mediated Fenton reaction in industrial waste water removal, we designed a iron-based polyphenol-coordinated nanomedicines for mild hyperthermia-assisted anti-cancer ferroustherapy. In brief, Fe-GA@BSA nanoparticles was synthesized by self-assembly and sorafenib(SRF) was loaded into Fe-GA@BSA to establish Fe-GA@BSA-SRF nanomedicines. The result nanomedicines can induce ferroptosis in cancer cells by accelerating Fenton reaction. And the photothermal effect of Fe-GA@BSA-SRF was used for mild hyperthermia-assisted ferroustherapy. The nanomedicines performs good anti-cancer therapeutic efficacy by inducing the production of ROS and inhibiting glutathione peroxidase 4(GPX4) expression in vitro and in vivo. Besides, the broad absorption of Fe-GA@BSA-SRF in near infrared region endows it with photoacoustic imaging ability. This study provides ideas about rational design on iron-based nanoparticles for anti-cancer ferroustherapy.展开更多
The development of nanomedicine systems for applications in cancer therapies has been widely explored in the last decade.With inherent biocompatibility,nanomedicine devices derived from biological membranes have shown...The development of nanomedicine systems for applications in cancer therapies has been widely explored in the last decade.With inherent biocompatibility,nanomedicine devices derived from biological membranes have shown many unique advantages compared with traditional artificial nanomaterials for biomedical applications.Herein,we present a comprehensive review of the recent development of cell membrane derived nanomedicines in cancer treatment.We firstly outline the advantages of biological membranes in nanomedicine design derived from their intrinsic characteristics,and then discuss the applications of biological membrane derived nanomedicines.For the first major category of membrane-derived nanomedicine,synthetic nanoparticles are usually camouflaged with cell membranes to acquire additional functionalities.The other type of membrane-based nanomedicine is directly using the engineered cell membrane-derived vesicles or nanovesicles secreted by cells for tumor treatment.At last,we discuss the challenges of membrane-derived nanomedicines towards future clinical applications,following with perspectives on possible solutions to the current problems.展开更多
文摘Immunotherapy and associated immune regulation strategies gained huge attraction in order to be utilized for treatment and prevention of respiratory diseases.Engineering specifically nanomedicines can be used to regulate host immunity in lungs in the case of respiratory diseases including coronavirus disease 2019(COVID-19)infection.COVID-19 causes pulmonary embolisms,thus new therapeutic options are required to target thrombosis,as conventional treatment options are either not effective due to the complexity of the immunethrombosis pathophysiology.In this review,we discuss regulation of immune response in respiratory diseases especially COVID-19.We further discuss thrombosis and provide an overview of some antithrombotic nanoparticles,which can be used to develop nanomedicine against thrombo-inflammation induced by COVID-19 and other respiratory infectious diseases.We also elaborate the importance of immunomodulatory nanomedicines that can block pro-inflammatory signalling pathways,and thus can be recommended to treat respiratory infectious diseases.
文摘Nanomedicines employ multiple endocytic pathways to enter cells.Their following fate is interesting,but it is not sufficient understood currently.This review introduces the endocytic pathways,presents new technologies to confirm the specific endocytic pathways and discusses factors for pathway selection.In addition,some intriguing implication about nanomedicine design based on endocytosis will also be discussed at the end.This review may provide new thoughts for the design of novel multifunctional nanomedicines.
基金This work was financially supported by the National Natural Science Foundation of China(81803443,81903551)the Natural Science Foundation of Zhejiang Province(LQ19H300001)+1 种基金the Wenzhou Science and Technology Bureau(ZY2019007,Y20180180,Y20180208,Y20190177)the start-up funds from the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University.
文摘Tumor cell usually exhibits high levels of reactive oxygen species and adaptive antioxidant system due to the metabolic,genetic,and microenvironment-associated alterations.The altered redox homeostasis can promote tumor progression,development,and treatment resistance.Several membrane transporters are involved in the resetting redox homeostasis and play important roles in tumor progression.Therefore,targeting the involved transporters to disrupt the altered redox balance emerges as a viable strategy for cancer therapy.In addition,nanomedicines have drawn much attention in the past decades.Using nanomedicines to target or reset the redox homeostasis alone or combined with other therapies has brought convincing data in cancer treatment.In this review,we will introduce the altered redox balance in cancer metabolism and involved transporters,and highlight the recent advancements of redox-modulating nanomedicines for cancer treatment.
文摘In recent years,nanomedicine plays an increasingly important role in improving the effectiveness,accuracy and safety of disease diagnosis and treatment.Happily,some of these nanoparticles are in clinical trials or have been approved by the Food and Drug Administration.With the deepening of research,people’s understanding of the interaction between nanomedicine and body system is increasing,and a new generation of biomimetic nanomedicine platforms has been developed to further improve the treatment effect of diseases.In this review,we will discuss recent advances in biomimetic nanosystems for the treatment of diseases,including cardio-cerebrovascular diseases,diabetes,and cancer.We hope that there will be more advanced biomimetic nanomedicines that can be widely used in the treatment of diseases in the future.
文摘Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune response.Numerous therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune response.However,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic response.Here,we outline the current state of using nanomedicines for boosting ICD of cancer cells.Moreover,synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were analyzed.We further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune responses.Endoplasmic reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicines,amplified reactive oxygen species(ROS)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative approaches.Various challenges,merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.
基金We are grateful to the National Natural Science Foundation of China(21934004,21627811)the National Key R&D Program of China(2021YFA0909400)the Natural Science Foundation of Fujian Province(2022J01329)for financial support.
文摘Lipid-based nanomedicines(LBNMs),including liposomes,lipid nanoparticles(LNPs)and extracellular vesicles(EVs),are recognized as one of the most clinically acceptable nano-formulations.However,the bench-to-bedside translation efficiency is far from satisfactory,mainly due to the lack of in-depth understanding of their physical and biochemical attributes at the single-particle level.In this review,we first give a brief introduction of LBNMs,highlighting some milestones and related scientific and clinical achievements in the past several decades,as well as the grand challenges in the characterization of LBNMs.Next,we present an overview of each category of LB-NMs as well as the core properties that largely dictate their biological characteristics and clinical performance,such as size distribution,particle concentration,morphology,drug encapsulation and surface properties.Then,the recent applications of several analytical techniques including electron microscopy,atomic force microscopy,fluorescence microscopy,Raman microscopy,nanoparticle tracking analysis,tunable resistive pulse sensing and flow cytometry on the single-particle characterization of LBNMs are thoroughly discussed.Particularly,the com-parative advantages of the newly developed nano-flow cytometry that enables quantitative analysis of both the physical and biochemical characteristics of LBNMs smaller than 40 nm with high throughput and statistical ro-bustness are emphasized.The overall aim of this review article is to illustrate the importance,challenges and achievements associated with single-particle characterization of LBNMs.
基金partially supported by grants from the National Natural Science Foundation of China (No.31971302,China)the Natural Science Foundation of Guangdong Province of China (No.2019A1515011597,China)+2 种基金the talent young scientist supporting program of China Association for Science and Technologythe Educational Commission of Guangdong Province of China Key Project (No.2020ZDZX2001,China)the joint grant between Guangzhou City and College (No.202102010106,China)。
文摘Atherosclerosis(AS)is a leading cause of the life-threatening cardiovascular disease(CVD),creating an urgent need for efficient,biocompatible therapeutics for diagnosis and treatment.Biomimetic nanomedicines(b NMs)are moving closer to fulfilling this need,pushing back the frontier of nano-based drug delivery systems design.This review seeks to outline how these nanomedicines(NMs)might work to diagnose and treat atherosclerosis,to trace the trajectory of their development to date and in the coming years,and to provide a foundation for further discussion about atherosclerotic theranostics.
基金financially supported by the National Natural Science Foundation of China(Nos.51988102,51833010,and 52273114)the Fundamental Research Funds for the Central Universities(No.PKU2022 XGK008).
文摘The complexity of the tumor microenvironment(TME)severely hinders the therapeutic effects of various cancer treatment modalities.The TME differs from normal tissues owing to the presence of hypoxia,lowpH,and immunesuppressive characteristics.Modulation of the TME to reverse tumor growth equilibrium is considered an effective way to treat tumors.Recently,polymeric nanomedicines have been widely used in cancer therapy,because their synthesis can be controlled and they are highly modifiable,and have demonstrated great potential to remodel the TME.In this review,we outline the application of various stimuli responsive polymeric nanomedicines to modulate the TME,aiming to provide insights for the design of the next generation of polymeric nanomedicines and promote the development of polymeric nanomedicines for cancer therapy.
基金financially supported by the Science and Technology Commission of Shanghai Municipality (No.21430760800,China)the National Natural Science Foundation of China (Nos.82273867,82030107,82241002,and 82073782)。
文摘Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment,nanomedicine designs have received widespread attention with significantly improved efficacy and reduced non-target side effects.Nanomedicines hold tremendous theranostic potential for treating,monitoring,diagnosing,and controlling various diseases and are attracting an unfathomable amount of input of research resources.Against the backdrop of an exponentially growing number of publications,it is imperative to help the audience get a panorama image of the research activities in the field of nanomedicines.Herein,this review elaborates on the development trends of nanomedicines,emerging nanocarriers,in vivo fate and safety of nanomedicines,and their extensive applications.Moreover,the potential challenges and the obstacles hindering the clinical translation of nanomedicines are also discussed.The elaboration on various aspects of the research trends of nanomedicines may help enlighten the readers and set the route for future endeavors.
基金supported by National Natural Science Foundation of China(Nos.U1903125,82073799)Natural Science Foundation of Hunan Province in China(Nos.2021JJ20084,2021JJ70016)the Science and Technology Innovation Program of Hunan Province(No.2021RC3020)。
文摘Sepsis is the leading cause of death in intensive care unit(ICU), which is caused by deregulated immune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and supportive care, while there still lacks of specific molecular therapy. As a type of immune dysfunction disease,macrophages have been recognized as the key immune cells precipitating in the whole process of sepsis,which is activated into M1-like to trigger various inflammatory responses at early stage whereas polarized into M2-like to cause immunosuppression in later stage. Therefore, great attention has been paid on the design of nanomedicines to regulate the functions of macrophages for etiological treatment of sepsis, by virtue of the unique advantages of nano-drug delivery systems, such as enhanced drug bioavailability, targetability, reduced side-effects. This critical review aims to summarize the recent progress of macrophages-regulating nanoparticles for sepsis therapy. First, the essential roles of macrophages in the development and progression of sepsis have been introduced, including the positive roles of macrophages to combat infections and dysfunction of macrophages to cause body damages. We then focus our main attention to discuss the nanomedicines with different therapeutic mechanisms corresponding to each stage of sepsis, such as infection blockage, inflammation inhibition, immune functions recovery, as well as multifunctional nanomedicines. Finally, a few limitations of current nanomedicines are highlighted,and future perspective are speculated for potential clinical translation, which might pave the way for the development of macrophages-centered nanomedicines for more effective sepsis therapy.
基金supported by the Basic Research Program of Science and Technology Commission of Shanghai Municipality(No.21JC1401800)。
文摘Nanomedicines have shown great promise in cancer therapy,but are challenged by limited drug loading,safety concerns of drug carriers,and complexity of function integration.Recently,carrier-free nanomedicines produced by supramolecular assembly of small-molecule therapeutic functionalities and their conjugates were proposed to address these issues.These nanomedicines achieve very high drug loading,enhanced tumor accumulation and improved therapeutic efficiency,and avoid carrier-related safety problems.In this review article,the applications of these nanomedicines in chemotherapy,photodynamic therapy,photothermal therapy as well as combination therapies will be reviewed.The concept of nanomedicine design and mechanism of supramolecular assembly will be discussed.Finally,future perspectives of carrier-free supramolecular nanomedicines for cancer therapy will be highlighted.
基金supported by the National Natural Science Foundation of China(No.32371458)the Key Research and Development Programs of the Ministry of Science and Technology(No.2022YFA1205700)+1 种基金the Basic Research Cooperation Special Foundation of Beijing-Tianjin-Hebei(Nos.H_(2)022205047,22JCZXJC00060,and E3B33911DF)funding from the National Center for Nanoscience and Technology and Chinese Academy of Sciences.
文摘RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases.These include antisense oligonucleotides(ASOs),small interfering RNAs(siRNAs),endogenous microRNAs(miRNAs),messenger RNAs(mRNAs),clustered regularly interspersed short palindromic repeats-associated protein 9(CRISPR/Cas9),single guide RNAs(sgRNAs),as well as RNA aptamers.These therapeutic agents exert their effects through various mechanisms such as gene inhibition,addition,replacement,and editing.The advancement of RNA biology and the field of RNA therapy has paved the way for the development and utilization of RNA-based nanomedicine in human healthcare.One remarkable example of RNA-based nanomedicine is the mRNA-based vaccines including mRNA-1273(Moderna)and BNT162b2(Pfizer/BioNTech)that have been successfully employed in response to the coronavirus disease 2019(COVID-19)pandemic.This review aims to highlight the advantages of RNA-based nanomedicines,provides an overview of significant developments in delivery systems,elucidates the molecular mechanisms of action underlying RNA-based nanomedicines,and discusses their clinical applications.Additionally,the review will address the existing challenges and innovations in delivery platforms while exploring the future possibilities for these promising RNA-based nanomedicines.
基金supported by the National Natural Science Foundation of China(No.82172186)the Zhejiang Provincial Natural Science Foundation of China(No.LY21H160030)+1 种基金the National Natural Science Foundation of China(No.82373206,No.82073332)the National Key Research and Development Program of China(No.2022YFE0107800).
文摘Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.
基金This study was supported by National Natural Science Foundation of China(82173762)111 Project(B18035,China)the Key Research and Development Program of Science and Technology Department of Sichuan Province(2022JDJQ0050,2022YFS0334).
文摘Cancer immunotherapy has significantly flourished and revolutionized the limited conventional tumor therapies,on account of its good safety and long-term memory ability.Discouragingly,low patient response rates and potential immune-related side effects make it rather challenging to literally bring immunotherapy from bench to bedside.However,it has become evident that,although the immunosuppressive tumor microenvironment(TME)plays a pivotal role in facilitating tumor progression and metastasis,it also provides various potential targets for remodeling the immunosuppressive TME,which can consequently bolster the effectiveness of antitumor response and tumor suppression.Additionally,the particular characteristics of TME,in turn,can be exploited as avenues for designing diverse precise targeting nanomedicines.In general,it is of urgent necessity to deliver nanomedicines for remodeling the immunosuppressive TME,thus improving the therapeutic outcomes and clinical translation prospects of immunotherapy.Herein,we will illustrate several formation mechanisms of immunosuppressive TME.More importantly,a variety of strategies concerning remodeling immunosuppressive TME and strengthening patients'immune systems,will be reviewed.Ultimately,we will discuss the existing obstacles and future perspectives in the development of antitumor immunotherapy.Hopefully,the thriving bloom of immunotherapy will bring vibrancy to further exploration of comprehensive cancer treatment.
基金Supported by Xi'an Jiaotong University Medical"Basic-Clinical"Integration Innovation Project,No.YXJLRH2022067Shaanxi Postdoctoral Research Program“Orlistat-loaded Nanoparticles as A Targeted Therapeutical Strategy for The Enhanced Treatment of Liver Cancer”,No.2023BSHYDZZ09.
文摘Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages,but it is often ineffective and suffers from problems such as multidrug resistance,rapid drug clearance,nonspecific targeting,high side effects,and low drug accumulation in tumor cells.In response to these limitations,recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC.This review focuses on recent advances in nanoparticle-based targeted drug delivery systems,with special attention to various receptors overexpressed on HCC cells.These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC.We comprehensively summarize the current understanding of these receptors,their role in nanoparticle targeting,and the impact of such targeted therapies on HCC.By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies,more effective and precise treatment of HCC can be achieved.
基金supported by the National Natural Science Foundation of China(No.82003661)。
文摘Increasing understanding of the pathogenesis of rheumatoid arthritis(RA)has remarkably promoted the development of effective therapeutic regimens of RA.Nevertheless,the inadequate response to current therapies in a proportion of patients,the systemic toxicity accompanied by longterm administration or distribution in non-targeted sites and the comprised efficacy caused by undesirable bioavailability,are still unsettled problems lying across the full remission of RA.So far,these existing limitations have inspired comprehensive academic researches on nanomedicines for RA treatment.A variety of versatile nanocarriers with controllable physicochemical properties,tailorable drug release pattern or active targeting ability were fabricated to enhance the drug delivery efficiency in RA treatment.This review aims to provide an up-to-date progress regarding to RA treatment using nanomedicines in the last 5 years and concisely discuss the potential application of several newly emerged therapeutic strategies such as inducing the antigen-specific tolerance,pro-resolving therapy or regulating the immunometabolism for RA treatments.
基金Financial supports by the National Natural Science Foundation of China(32071385,31771092,31930066)Shandong Provincial Natural Science Foundation of China(ZR2019ZD25)Fudan-SIMM Joint Research Fund(FU-SIMM20182005,China)。
文摘Compared with traditional drug therapy,nanomedicines exhibit intriguing biological features to increase therapeutic efficiency,reduce toxicity and achieve targeting delivery.This review provides a snapshot of nanomedicines that have been currently launched or in the clinical trials,which manifests a diversified trend in carrier types,applied indications and mechanisms of action.From the perspective of indications,this article presents an overview of the applications of nanomedicines involving the prevention,diagnosis and treatment of various diseases,which include cancer,infections,blood disorders,cardiovascular diseases,immuno-associated diseases and nervous system diseases,etc.Moreover,the review provides some considerations and perspectives in the research and development of nanomedicines to facilitate their translations in clinic.
基金This work was supported by the National Natural Science Foundation of China(51873120,51673127,81621003)National Science and Technology Major Project of China(2017ZX09304023)+1 种基金Ruilong Sheng,Helena Tomas and Joao Rodrigues appreciate the support from Fundaçao para a Ciencia e a Tecnologia(Base Fund UIDB/00674/2020,CQM,Portuguese Government Funds)ARDITI-Agencia Regional para o Desenvolvimento da Investigaçao Tecnologia e Inovaçao through the project M1420-01-0145-FEDER-000005-Centro de Química da Madeira-CQM+(Madeira 14-20 Program)and ARDITI-2017-ISG-003.
文摘Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics.However,direct administration of“naked”immunotherapeutic agents(such as nucleic acids,cytokines,adjuvants or antigens without delivery vehicles)often results in:(1)an unsatisfactory efficacy due to suboptimal pharmacokinetics;(2)strong toxic and side effects due to low targeting(or off-target)efficiency.To overcome these shortcomings,a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects.Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties,as they could interact with immune system to stimulate an enhanced immune response.Their structures offer versatility in synthesizing multifunctional nanocomposites,which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues.This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics.
基金supported by grants from the National Natural Science Foundation of China (No. 51903062)Guangdong Basic and Applied Basic Research Foundation (No.2020A1515011320)+1 种基金Science and Technology Projects of Guangzhou(No. 202102020757)Subject Construction Project of Basic Medical Sciences of Guangzhou Medical University (Nos.JCXKJS2021B07, JCXKJS2021D09)。
文摘Ferroustherapy has gained great attention for anti-cancer treatment in recent years. Enlightened by temperature-mediated Fenton reaction in industrial waste water removal, we designed a iron-based polyphenol-coordinated nanomedicines for mild hyperthermia-assisted anti-cancer ferroustherapy. In brief, Fe-GA@BSA nanoparticles was synthesized by self-assembly and sorafenib(SRF) was loaded into Fe-GA@BSA to establish Fe-GA@BSA-SRF nanomedicines. The result nanomedicines can induce ferroptosis in cancer cells by accelerating Fenton reaction. And the photothermal effect of Fe-GA@BSA-SRF was used for mild hyperthermia-assisted ferroustherapy. The nanomedicines performs good anti-cancer therapeutic efficacy by inducing the production of ROS and inhibiting glutathione peroxidase 4(GPX4) expression in vitro and in vivo. Besides, the broad absorption of Fe-GA@BSA-SRF in near infrared region endows it with photoacoustic imaging ability. This study provides ideas about rational design on iron-based nanoparticles for anti-cancer ferroustherapy.
基金This work was partially supported by the National Research Programs from Ministry of Science and Technology of China(2016YFA0201200)the National Natural Science Foundation of China(21907073,52032008)+1 种基金the Jiangsu Social Development Project(BE2019658)Collaborative Innovation Center of Suzhou Nano Science and Technology,the “111” program from the Ministry of Education of China and the Key Scientific and Technological Projects of Henan Province of China(192102310071).
文摘The development of nanomedicine systems for applications in cancer therapies has been widely explored in the last decade.With inherent biocompatibility,nanomedicine devices derived from biological membranes have shown many unique advantages compared with traditional artificial nanomaterials for biomedical applications.Herein,we present a comprehensive review of the recent development of cell membrane derived nanomedicines in cancer treatment.We firstly outline the advantages of biological membranes in nanomedicine design derived from their intrinsic characteristics,and then discuss the applications of biological membrane derived nanomedicines.For the first major category of membrane-derived nanomedicine,synthetic nanoparticles are usually camouflaged with cell membranes to acquire additional functionalities.The other type of membrane-based nanomedicine is directly using the engineered cell membrane-derived vesicles or nanovesicles secreted by cells for tumor treatment.At last,we discuss the challenges of membrane-derived nanomedicines towards future clinical applications,following with perspectives on possible solutions to the current problems.